Ingestible films having substances from hemp or cannabis

ABSTRACT

Films that are mucosally dissolvable, and containing a matrix and one or more active agents from hemp or  cannabis  within the matrix, are provided. The disclosure also provides methods for preparing such a film for pharmaceutical and nutraceutical applications.

RELATED U.S. APPLICATION DATA

This application claims priority to and is a continuation of U.S. patentapplication Ser. No. 15/485,655 filed Apr. 12, 2017 which claims thebenefit of priority to U.S. Provisional Patent Application Ser. No.62/32,480 filed on Apr. 12, 2016 and U.S. Provisional Application PatentApplication Ser. No. 62/338,762 filed on May 19, 2016, the entirecontents of each of these applications are incorporated herein byreference.

FIELD OF INVENTION

The present disclosure relates to mucosally dissolvable films containingone or more active substances, such as those obtained from hemp and/orcannabis, and methods of making such films for pharmaceutical ornutraceutical applications.

BACKGROUND

The Cannabis plant has a long history of medicinal use. The beneficialcompounds in cannabis are used by patients to alleviate the side effectsand symptoms of countless medical conditions, including pain, cancer,HIV, AIDS, multiple sclerosis, glaucoma, and more.

The cannabis compounds are generally administered by inhalation of smokeor vapors, ingestion of edible capsules or liquid extracts such astinctures or oils, use of topical solutions and ingestible films orwafers. But each mode of delivery has its own disadvantages. Forexample, the current delivery systems of smoking, and vaporizing areunhealthy, inconvenient and lack proper dosage control. Oraladministration of cannabis, like any medication is not always“fast-acting”, a property clearly desirable in the treatment of acutebreakthrough pain, for example. Besides, some pediatric and/or geriatricpatients have difficulty taking an oral medication due to inability toswallow, nausea or other gastrointestinal problems. While liquid, syrupsor suspensions are an alternative to solid dosage forms, suchformulations often deteriorate rapidly upon exposure to heat or otheratmospheric conditions and consequently have a relatively short shelflife. The films or wafers containing cannabis extracts are often verysticky, have a bitter after-taste and hence can contribute to patientnon-compliance. In addition, conventional thin films or wafers often donot include a high load of the active ingredient.

SUMMARY

In one embodiment, a film includes an emulsion of an extract ofcannabis, pullulan, hydroxypropylmethyl cellulose acetate succinate, anda flavorant or taste masking agent. The film is mucosally dissolvable.

In another embodiment, a film includes an emulsion of an extract ofcannabis, pullulan, hydroxypropylmethyl cellulose acetate succinate,pectin, guar gum, medium chain triglycerides from coconut oil, and aflavorant or taste masking. The film is mucosally dissolvable.

In another embodiment, a film includes an emulsion of an extract ofcannabis, pullulan, hydroxypropylmethyl cellulose acetate succinate,pectin, guar gum, and coconut oil or medium chain triglycerides. Thefilm also includes vanilla, bubble gum, fruit flavor, mint, chocolate,licorice, marshmallow, peanut butter, aspartame, sucralose, sucrose,glucose, citric acid, stevia plant, kleptose, cyclodextrin, cyclodextrinderivatives, ginger, anise, cinnamon, peppermint, licorice, fruit juice,sweeteners, fructose, mannitol, saccharin, or honey. The film ismucosally dissolvable.

In various embodiments, the thin mucosally dissolvable film described inthis disclosure contains high loading dose of purified active ingredientfrom cannabis, is easily penetrable through mucosal tissue, has improvedtaste profile, and is non-sticky.

The thin, mucosally dissolvable film may contain a matrix and an activeagent dispersed uniformly in the matrix. The active agent being anextracted substance from cannabis or hemp, may include cannabinoids(CBD) or tetrahydrocannabinol (THC) in concentrations greater than about90% and up to about 100%. When the active agent is CBD, then it may bepresent in a concentration of at least 90% and up to about 100%, withlittle or no trace of THC. When the active agent is THC, then it may bepresent in a concentration of at least 90% and up to about 100%, withlittle or no trace of CBD. The active agent may be present in the filmfrom about 1% to about 70% by weight. The extracted substance fromcannabis or hemp may exist in the form of an isolate, which is powderlike and is light yellow in color. The extracted substance may alsoexist in the form of an emulsion without waxes and oils, oil, paste,liquid, resin, crystal, powder, or pulp.

The thin film may additionally include permeability enhancers in amountsfrom about 0.001% to about 10% by weight of the film and may be selectedfrom the group of one or more calcium chelators, polycarboxylic acids,zonula occluding toxin, poly-L-arginine, chitosan derivatives, niacin,omega 3 or 6 fatty acids or other fatty acids, menthol, sodium caprate,sodium deoxycholate, dipotassium glycyrrhizinate, 25 furanocoumarins andgrapefruit derivatives, bile salts, ethylenediaminetetraacetic acid(EDTA), tocopheryl polyethyleneglycol succinate (TPGS), derivativesthereof, and combinations thereof, or the like.

Since the CBD and THC have a very bitter taste, the film may alsocontain one or more taste masking agents or bitter blockers. The amountof the taste masking agents may range from about 0.001% to about 0.5% byweight of the film and may be selected from the group of kleptose,cyclodextrin, cyclodextrin derivatives, ginger, anise, cinnamon,peppermint, licorice, fruit juice, sweeteners, sucrose, glucose,fructose, mannitol, saccharin, aspartame, sucralose, stevia plantderivatives, honey, or any combination thereof.

The matrix containing the active agent may be formed from an ediblepolymer that is natural such as, but not limited to, methylcellulose,hydroxypropylmethylcellulose, ethylcellulose, sodium alginate, starch,chitosan, chitin, pullalan, agar, derivatives and/or combinationsthereof. The matrix may also be formed from synthetic polymersincluding, but not limited to, hydroxyethylcellulose, cellulose acetatephthalate, hydroxypropyl methylcellulose phthalate, carboxymethylethylcellulose, hydroxypropylmethyl cellulose acetate succinate,polyvinyl acetate phthalate, maltodextrin, dextran, hydroxypropylcellulose, sodium carboxymethyl cellulose, poly(methacrylicacid-co-ethyl acrylate), poly(methacrylic acid-co-methyl methacrylate),poly(methacrylic acid-co-ethyl acrylate), poly(methacrylicacid-co-methyl methacrylate), polyvinylpyrrolidone, polylactic acid(PLA), poly-L-lactide (PLLA), poly-D-lactide (PLDA),poly(lactic-co-glycolic acid) (PLGA), and mixtures thereof.

The matrix may further contain additional compounds selected from thegroup of a solubilizer, a thickener, a surfactant, a coloring agent, aflavorant, an effervescent agent, an antioxidant, a bioadhesive agent, apH modifying agent, vitamins, minerals, a dietary supplement, one ormore of different strains of cannabidiol from plants, anti-inflammatorysubstances, steroids, medicaments, cosmetic components, pharmaceutical,nutraceutical, or mixtures thereof.

The film of the present disclosure may be prepared from any methodincluding, but not limited to, solution casting, spin coating,extrusion, calendaring, roll-pressing, microfabrication, molding jetprinting, drop-on demand printing, dot, printing, etc. The resultingfilm product may have a thickness ranging from about 0.1 mils to about30 mils.

Generally, the method of preparing a thin mucosally dissolvable filminclude the steps of: (a) providing an active agent, which is anextracted substance obtained from cannabis or hemp, and includescannabinoids (CBD) or tetrahydrocannabinol (THC) in concentration of atleast 90% and up to about 100%. (ii) dissolving the active agent in asolvent mixture; (iii) forming a homogenous emulsion of the active agentand solvent mixture at temperatures ranging from about 70° F. to about380° F.; (iv) adding a sugar polymer and additives to the homogenousemulsion to form a modified emulsion; (v) casting the modified emulsioninto a film, and (vi) drying the film.

The method may further include packaging the dried film with foils oneach side to form a single packet.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic representation of a thin film showing theactive agent dissolved in the matrix;

FIG. 2 is another embodiment of the film with insoluble active agentimpregnated in the film matrix;

FIG. 3 is a diagrammatic representation of the film cast on a wax orsilicon substrate;

FIG. 3A is a diagrammatic representation of the film that is disposedbetween two protective foils;

FIG. 3B is a diagrammatic representation of the film that is disposedbetween two protective foils combined with poly layers creatingindividual sealed pouch package;

FIG. 4 illustrates a method for preparing an oral film, in variousembodiments;

FIG. 5 is a graphic representation of a casting process for preparing athin mucosally dissolvable film;

FIG. 6 is a graphic representation of an extrusion process for preparingthe thin film;

FIG. 7 is a graphic representation of a molding process for preparingthe thin film.

DETAILED DESCRIPTION

The present disclosure is not limited in terms of the particularembodiments described in this application, which are intended asillustrations of various aspects only. Many modifications and variationscan be made without departing from the scope of the invention, as willbe apparent to those skilled in the art. Functionally equivalent methodswithin the scope of the disclosure, in addition to those enumeratedherein, will be apparent to those skilled in the art from the followingdescriptions. Such modifications and variations are intended to fallwithin the scope of the appended claims. It is also to be understoodthat the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to be limiting.

As will be understood by one skilled in the art, for any and allpurposes, such as in terms of providing a written description, allranges disclosed herein also encompass any and all possible subrangesand combinations of subranges thereof. Any listed range can be easilyrecognized as sufficiently describing and enabling the same range beingbroken down into at least equal halves, thirds, quarters, fifths,tenths, etc. As a non-limiting example, each range discussed herein canbe readily broken down into a lower third, middle third and upper third,etc. As will also be understood by one skilled in the art, all languagesuch as “up to,” “at least,” and the like include the number recited andrefer to ranges which can be subsequently broken down into subranges asdiscussed above. Finally, as will be understood by one skilled in theart, a range includes each individual member. Thus, for example, a grouphaving 1-3 cells refers to groups having 1, 2, or 3 cells.

Generally, the present invention is related to mucosally dissolvablefilm having an active agent. The “active agent” may include one or moresubstances, such as cannabinoids or cannabidiol (CBD) ortetrahydrocannabinol (THC) obtained from hemp and/or cannabis. The“active agent” may also include an extracted substance from hemp orcannabis such as the CBD or THC, in addition to other biologicallyactive substances such as, but not limited to, drugs or medicaments,nutraceuticals, pharmaceutical that can alleviate a symptom in a subjectin need thereof. In another aspect, the active agent refers to only thebiologically active agents such as drugs or medicaments, nutraceuticals,pharmaceutical that can alleviate a symptom in a subject in needthereof.

The “films” or “wafers” or “sheets” can be any type of film that can beadministered to a subject to provide the substance or mixture ofsubstances from hemp or cannabis or other biologically active agentssuch as a medicament or a pharmaceutical or a nutraceutical. In oneexample, the films may be sublingual or orally dissolving films ormucosally dissolving films, that are edible and pharmaceuticallyacceptable. A “mucosally dissolvable film” refers to any thin film thatallows an active agent to seep or absorb through the mucosal membrane ofany mammalian subject. It is not the same as any oral film that isswallowed such that the film components, including the active agent,traverses the digestive tract of the subject. The mucosal transmissionof the active agent in the present disclosure is enabled by the lipidbased emulsion system and/or the penetration enhancers and buffer systememployed during the preparation of the film. It will be appreciated thatany other type of film may be used such as those that are allowed todissolve or absorb in a mouth, vagina or rectum. The films of thepresent disclosure may also adhere to any mucosal tissue of a subject ormay also adhere to skin of a subject.

Also, the present disclosure is related to methods of making emulsionshaving the substance or mixture of substances from hemp or cannabis, anduse of the emulsions for making the mucosally dissolvable films.

Active Agents

The substance or mixture of substances may be obtained from hemp orcannabis in any form. That is, the one or more substances may be in anycomposition format, such as an oil or wax extract, or paste, any liquidformat, resin, crystal, powder, isolate or pulp form. Previously, it hasbeen found to be difficult to incorporate oils or extracts from hemp orcannabis into a uniform and consistent composition to preparedissolvable films that can be reliably produced across batches.Typically, such sources of substances are very hydrophobic in nature,and thus do not mix or dissolve into water, thereby making it ratherdifficult to incorporate the oils or waxes into materials, such asdissolving films.

In this disclosure, the extracted substance or the active agent (e.g.,CBD or THC) is the main constituent of the films described herein,wherein the active agent can exist as 0.1% to 90% of such obtainedsubstances. Specifically, the extracted substance or active agent (e.g.,CBD or THC) may be in a purified form such that the concentration of theCBD or THC is greater than 90%, greater than 95%, greater than 98% orgreater than or about 99%. The purified substances, if used in thepreparation of the film, may also be purchased from manufacturers. Forexample, the commercially available Elixinol 99.4% Hemp extract isolate,EX-513W contains 90-100% CBD and no THC and it may be suitable for thepreparation of the film of the present disclosure. Similarly, an extractcontaining more than 90% of THC and little or no CBD may be purchasedfrom CLEAR. It will be appreciated that using such high concentration ofpurified CBD is advantageous because, a film with a higher loadingdosage can be prepared with lower amounts of purified substances. Forexample, a film formulation may include an extract from cannabis havingat least 90% and up to about 100% CBD and may be present in the filmfrom about 1% to about 70% by weight of the film. On the other hand, ifless purified substances such as a raw extract from cannabis or hempcontaining less than 35% CBD is used, then to achieve the same highloading dosage more than 90% of CBD may be needed in the film.Additionally, using higher concentrations such as >90% of CBD or THCisolate in a film of the present disclosure would prevent the bittertaste of flavonoids or other raw plant materials from cannabis or hemp.It will be understood that the extracted substance may also be used in aless purified form such that the concentration of CBD or THC is lessthan about 90%, about 70%, about 60%, about 50%, about 30%, or about15%.

The agent (e.g., substance from hemp and/or cannabis) may be preparedinto an emulsion that if formed into a film, such as an orallydissolving film, the agent may be present from less than 1% to greaterthan 60% by weight of the film.

The substance obtained from hemp or cannabis may be a wax or oil orpaste or other format and may have a concentration from about 0.1% toabout 90%. Such composition can be the source of the substance ormixture of substances. CBD wax may come from industrial hemp orcannabis, with CBD ranging in a concentration of 0.1% to 90%, which isusually a viscous extract containing various amounts of CBD, anddepending on extraction method and material source (industrial hemp orcannabis) may contain varying amounts of additional plant material suchas chlorophyll, terpenes or THC. CBD extract may be extracted usingvarious methods, one method is to use carbon dioxide which may preventadditional unwanted substances in the final product. Other methods thatmay be used to extract CBD from hemp include ethanol and oil extraction.CBD oil may come from industrial hemp or cannabis, with CBD ranging in aconcentration of 0.1% to 90%, which is typically less viscous thanwaxes, oils may be extracted in various ways and contain varying amountsof CBD and other plant extracts such as chlorophyll, terpenes and THC.CBD oil may be extracted using carbon-di-oxide in a similar way to thegeneration of CBD wax. Additionally, ethanol or oil may be used tocreate a CBD oil.

The commercially available CBD oil such as ELIXINOL 35% CBD Hemp Oil,EX-AMBR-21 (Raw and decarbed) which contains 31-5% to 38.5% CBD and1.05% to 1.2% THC or ELIXINOL 4% CBD Hemp Oil, EX-213 (Raw and Decarbed)containing 3.6% to 4.4% CBD and 0% THC or ELIXINOL 17.4% CBD Hemp Oil,EX-913 (Raw and decarbed) containing 15.7% to 19.1% CBD and only a traceamount of THC (0.51%) may be used in the preparation of the films of thepresent disclosure.

The active agent 104 or drug may be used as fine particles (shown inFIG. 1) or the drug can be agglomerated alone with an agglomeratingagent into particles. The resulting particles may then be suspended inthe film sheet carrier matrix (e.g., polymer matrix). While some drugsmay be in a particle format that is suspended 304 in the carrier matrix302 as shown in FIG. 2, some drugs can be dissolved in the carriermatrix (see FIG. 1). The particles can be micro- and/or nanoparticles.The particles can be microspheres, liposomes, micelles, or otheragglomeration of molecules. When the active agent is in a nanoparticlesize or single molecule, such as less than about 500 nm, it may becombined with a water-soluble polymer composition to form aself-supporting film in accordance with the present disclosure. However,the CBD and/or THC may be in the form of particles, such as in a powder.

The film may be prepared to have a specific amount of biologicallyactive agent, such as a specific amount of drug. The amount of drugincluded should be consistent across a number of batches so that theingestible unit can achieve regulatory compliance. Accordingly, themethod of preparing an ingestible unit can include: preparing acomposition having a biologically active agent at a defined amount;forming the composition into a discrete sheet to have the biologicallyactive agent at a defined amount; and including the discrete sheet in apackage. The method may also include: determining a dose of abiologically active agent to be included in a film. Drug loading intosheets may be up to about 70% by weight of the sheet, and often up toabout 50% by weight. The amount of drug in each sheet can be calculatedbefore or after shaping the individual sheets or ingestible unit intothe size and shape of the dosage form. The amount of drug lost duringprocessing can also be taken into account in order to design theingestible units and select the appropriate number of sheets to arriveat the predetermined dose.

However, it should be recognized that a single sheet may be suitable forthe entire dose of an ingestible unit. The same methodologies can beperformed when the ingestible unit includes two or more differentbiologically active agents. Moreover, this methodology can be used fordetermining the amount of any agent or ingredient described herein.

Other Components of the Film

In addition to the active agents obtained from Cannabis or Hemp and/or abiological drug, the film of the present disclosure may also containpermeability or penetration enhancers or absorption enhancers to improvethe absorption of the active agent by the mucosal tissues of a subject,and taste-masking agents or bitter blockers to mask the bitter taste ofCBD or THC. The penetration enhancers may include compounds such as, butnot limited to, calcium chelators such as EOTA, polycarboxylic acids,zonula occluding toxin, poly-L-arginine, chitosan derivatives, niacin,omega 3 or 6 fatty acids or other fatty acids, menthol, sodium caprate,sodium deoxycholate, dipotassium glycyrrhizinate, 25 furanocoumarins andgrapefruit derivatives, bile salts, ethylenediaminetetraacetic acid,tocopheryl polyethyleneglycol succinate (TPGS), derivatives thereof, andcombinations thereof, or the like. These penetration or absorptionenhancers may be present in an amount ranging from 0.001% to about 10%by weight of the film. The preferred amount of penetration enhancer inthe film may range from about 0.1% to about 3% by weight of the film.

The taste-masking agent on the other hand, may be selected fromkleptose, cyclodextrin, cyclodextrin derivatives, ginger, anise,cinnamon, peppermint, licorice, fruit flavoring, citric acid, fruitjuice, sweeteners, sucrose, glucose, fructose, mannitol, saccharin,aspartame, sucralose, Stevia plant derivatives, honey, derivativesthereof, and combinations thereof. The amount of the taste-maskingagents or bitter blockers in the film may range from about 0.001 to 5%by weight of the film, preferably from 0.001 to 0.5% by weight of thefilm.

The film may further include one or more components in the matrix suchas, but not limited to, a film-forming agent; a filler; a plasticizer; ataste-masking agent; a coloring agent; a solubilizing agent; aneffervescent agent; an antioxidant; an absorption enhancer; adisintegrating agent; a pH modifying or buffer agent; a surfactant; acomplexing agent; a bio-adhesive agent; a sheet adhesive; an identifyingagent; an anti-counterfeiting agent; a tracking agent; transporterinhibitor agent; transporter inducer agent; emulsifying agent,self-emulsifying system agents; crystallization inhibitor;crystallization promoter; super-saturation promoting agent;antimicrobial preservative; catalyst; chelating agent; particles;organoleptic agent; flavoring agent; scent agent; identifying device;and/or anti-counterfeiting device. These types of ingredients can beexemplified by substances that are commonly used for pharmaceuticalcompositions or other ingestible compositions. Preferably, these typesof ingredients are defined as generally recognized as being safe (GRAS)by a government agency, such as the U.S. FDA. In one embodiment, theingredients can be defined as being approved by a select committee onGRAS substances (SCOGS), such as which can be found at the U.S. FDAwebsite, which is incorporated herein by specific reference in itsentirety, specifically included is the GRAS and SCOGS ingredients.

The film of the present disclosure may also be prepared from agentsselected from methylcellulose, hydroxypropylmethylcellulose,ethylcellulose, sodium alginate, poly (methacrylic acid-co-ethylacrylate), poly (methacrylic acid-co-methyl methacrylate), starch, 30polyvinylpyrrolidone, polylactic acid (PLA), poly-L-lactide (PLLA),poly-D-lactide (PLDA), poly (lactic-co-glycolic acid) (PLGA), chitosan,chitin, pullulan, derivatives thereof, and combinations thereof. Theplasticizer when used in the preparation of the film may be selectedfrom glycerine, triacetin, triacetyl citrate, polyethyleneglycol,mineral oil, myglyol, derivatives thereof, and combinations thereof.

The film compositions may further include food colorants, such ascarotenoid compounds and FD&C red, green, yellow, and blue, or the like.The solubilizing agent can be selected from polyvynilpyrrolidone,polyvinylcaprolactam-polyvinylacetate-polyethyleneglycol copolymer,fatty acids, castor oil, cyclodextrins, polyethyleneglycol, glyceryldistearate, lecithin, monoglycerides, diglycerides, triglycerides,propylene glycol monostearate, Labrafils (e.g., oleoyl macrogol-6glycerides, oleoyl polyoxyl-6-glycerides, linoleoyl macrogol-6glycerides, linoleoyl polyoxyl-6 glycerides, lauroyl macrogol-6glycerides, lauroyl polyoxyl-6 glycerides), Labrasols (e.g.,caprylocaproyl macrogol-8 glycerides, caprylocaproyl polyoxyl-8glycerides), Solutols (e.g., poly-oxyethylene esters of12-hydroxystearic acid), Soluplus (e.g., polyvinyl caprolactam-polyvinylacetate-polyethylene glycol graft co-polymer), derivatives thereof, andcombinations thereof. Soluplus can also be used as a film-forming agent.

The effervescent agent may be selected from sodium carbonate,bicarbonate, potassium carbonate, calcium carbonate, citric acid, malicacid, tartaric acid, adipic acid, fumaric acid, derivatives thereof, andcombinations thereof.

The antioxidant, if present in the film, may be selected fromtocopherol, vitamin E, resveratrol, ascorbyl palmitate,tert-butylhydroquinone, resveratrol, nordihydroguaiaretic acid,cysteine, propyl gallate, octyl gallate, 3-tert-butyl-4-hydroxyanisole,butylated hydroxytoluene, ascorbic acid, derivatives thereof, andcombinations thereof, or the like.

The disintegrating agent may be selected from croscarmellose sodium,sodium starch glycolate, insoluble polyvinylpyrrolidone,carboxymethylcellulose, derivatives thereof, and combinations thereof,or the like.

The film may also include pH modifier or buffer agent selected fromsodium carbonate, magnesium carbonate, calcium carbonate, sodiumhydroxide, potassium hydroxide, ascorbic acid, citric acid, succinicacid, fumaric acid, derivatives thereof, and combinations thereof.

The surfactant in the film may be selected from sodium lauryl sulfate,poloxamers, sorbitan esters, polysorbates, sorbitans, stearic acid,derivatives thereof, and combinations thereof.

The complexing agent, if present in the film, may be selected fromcyclodextrins, calcium glycerophosphate, dodecyl 2-(N,N-dimethylamino)propionate, zinc, dextran, pectin, copper acetate, sodium deoxycholate,calcium, magnesium, derivatives thereof, and combinations thereof.

The bio-adhesive agent, if present in the film, may be selected fromgelatin, starch, glycoproteins, proteins, carbohydrates,mucopolysaccharides, derivatives thereof, and combinations thereof.

The sheet adhesive, if present in the film, may be selected frompolyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate,confectionary glue, starch, derivatives thereof, or combinationsthereof.

The tracking agent, identifying agent, or anti-counterfeiting agent, ifpresent in the film, may be selected from fluorescein, rhodamine,succinimidyl esters, maleimide activated fluorophores, fluorescent dyes,fluorescent particles, infrared active particles, near infrared activeparticles, metallic nanoparticles, polymeric particles, silica basednanoparticles, SERS (Surface Enhanced Raman Spectroscopy) particles,raman active particles, derivatives thereof, and combinations thereof.

The osmotic agent, if present in the film, may be selected frommannitol, osmitrol, dextrose, sucrose, fructose, sodium chloride,potassium chloride, xylitol, sorbitol, lactose, potassium phosphate,derivatives thereof, or combinations thereof.

The transporter inhibitor, if present in the film, may be selected fromelacridar, zosuquidar, glibenclamide, quinaxoline derivatives,phenylalanine, arginyl naphthylamide, grapefruit derivatives,furanocoumarins, derivatives thereof, and combinations thereof. Thetransporter inducer, if present in the film, may be selected fromxenobiotics, diallyl sulfide, dexamethasone, derivatives thereof, andcombinations thereof.

The emulsifying agent, if present in the film, may be selected fromtocopheryl polyethyleneglycol succinate (TPGS), Cremophor (e.g.,non-ionic polyethoxylated detergents), Lutrol (e.g., polyethyleneglycol), Poloxamers (e.g., polyethylene-polypropylene glycol),cholesterol, octyldodecanol, polyoxylglycerides, derivatives thereof,and combinations thereof.

The self-emulsifying system may be selected from Labrasol, Labrafil,Cremophor, Pluronics, Lutrol, poloxamers, polysorbates, ethyl linoleate,mono- and diglycerides of capric and caprylic acids, tocopherol acetate,Solutol, soybean oil, tocopheryl polyethyleneglycol succinate (TPGS),Capmuls, derivatives thereof, and combinations thereof, or the like.

Crystallization inhibitors, if present in the film, may be selected frompolyvinylpyrollidone, hydroxypropylmethylcellulose, silicon dioxide,dextrins, dextrans, bile acids, sterols, polysebacic anhydride,derivatives thereof, and combinations thereof.

The supersaturating promoting agent, if present in the film, may beselected from hydroxyproylmethylcellulose, hydroxypropylmethylcelluloseacetate succinate, polyvinylpyrollidone, derivatives thereof, andcombinations thereof.

The antimicrobial preservative, if present in the film, may be selectedfrom benzoic acid, sodium benzoate, methyl paraben, propyl baraben,butyl paraben, sorbic acid, propionic acid, dehydroacetic acid,derivatives thereof, and combinations thereof. The catalyst may beselected be heavy metals selected from Ni, Cr, Mn, Zn, Fe, orcombinations thereof, or the like.

An organoleptic agent may be a flavorant or scent, such as selected fromvanilla, bubble gum, fruit flavor, mint, chocolate, licorice,marshmallow, peanut butter, aspartame, sucralose, sucrose, glucose,citric acid, stevia plant, derivatives thereof, or combinations thereof.The organoleptic agent for a veterinary embodiment can be selected fromglutamates, chicken flavor, umami flavoring, beef flavor, fish flavor,or the like. The chelating agent, if present in the film, may beselected from disodium edetate, EDTA, pentetic acid, derivatives thereofand combinations thereof.

Starches such as corn starch, potato starch, pregelatinized and modifiedstarches thereof, cellulosic agents such as Act-di-sol, montmorriloniteclays including cross-linked PVP, sweeteners, bentonite and VEEGUM™,microcrystalline cellulose, alginates, sodium starch glycolate, gumssuch as agar, guar, locust bean, karaya, pecitin and tragacanth may alsobe included in the film. Disintegrants may comprise up to about 20weight percent and preferably between about 2 and about 5 percent of thetotal weight of the composition.

The film may also include surfactants such as sodium lauryl sulfate,sodium dodecyl sulfate and tween; bile salts such as sodiumtaurocholate; fatty acids such as oleic and linoleic acid; andnon-surfactants such as AZONE and dialkyl sulfoxides.

Coloring agents may also be present in the film and could includetitanium dioxide, and dyes suitable for food such as those known as F.D.& C. dyes and natural coloring agents such as grape skin extract, beetred powder, beta-carotene, annato, carmine, turmeric, paprika, etc. Thecoloring agent, if present in the film, may range from about 0 to about2.5 weight percent of the total composition.

Flavors incorporated in the composition may be chosen from syntheticflavor oils and flavoring aromatics and/or natural oils, extracts fromplants, leaves, flowers, fruits and so forth and combinations thereof.These may include cinnamon oil, oil of wintergreen, peppermint oils,clove oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leave oil,oil of nutmeg, oil of sage, oil of bitter almonds and cassia oil. Alsouseful as flavors are vanilla, citrus oil, including lemon, orange,grape, lime and grapefruit, and fruit essences, including apple, pear,peach, strawberry, raspberry, cherry, plum, pineapple, apricot and soforth. Flavors which have been found to be particularly useful includecommercially available orange, grape, cherry and bubble gum flavors andmixtures thereof. The amount of flavoring may depend on a number offactors, including the organoleptic effect desired. Flavors may bepresent in an amount ranging from about 0.5 to about 3.0 by weight basedupon the weight of the composition. Particularly preferred flavors arethe grape and cherry flavors and citrus flavors such as orange.

Vitamins may be included and refers to trace organic substances that arerequired in the diet. For the purposes of the present invention, theterm vitamin(s) include, without limitation, thiamin, riboflavin,nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid,vitamin B12, lipoic acid, ascorbic acid, vitamin A, vitamin D, vitamin Eand vitamin K. Also included within the term vitamin are the coenzymesthereof. Coenzymes are specific chemical forms of vitamins. Coenzymesinclude thiamine pyrophosphates (TPP), flavin mononucleotide (FMM),flavin adenine dinucleotive (FAD), nicotinamide adenine dinucleotide(AND), nicotinamide adenine dinucleotide phosphate (NADP), Coenzyme A(CoA), pyridoxal phosphate, biocytin, tetrahydrofolic acid, coenzymeB12, lipoyllysine, 11-cis-retinal, and 1,25-dihydroxycholecalciferol.The term vitamin(s) also includes choline, carnitine, and alpha, beta,and gamma carotenes. A mineral may be used in the films, and refers toinorganic substances, metals, and the like required in the human diet.Thus, the term “mineral” as used herein includes, without limitation,calcium, iron, zinc, selenium, copper, iodine, magnesium, phosphorus,chromium and the like, and mixtures thereof.

The film may also include a dietary supplement, which is a substancewhich has an appreciable nutritional effect when administered in smallamounts. Dietary supplements include, without limitation, suchingredients as bee pollen, bran, wheat germ, kelp, cod liver oil,ginseng, and fish oils, amino-acids, proteins and mixtures thereof. Aswill be appreciated, dietary supplements may incorporate vitamins andminerals.

The film may further include binders such as but not limited to acacia,tragacanth, gelatin, starch, cellulose materials such as methylcellulose and sodium carboxymethyl cellulose, alginic acids and saltsthereof, polyethylene glycol, guar gum, polysaccharide, sugars, invertsugars, poloxomers (PLURONIC F68, PLURONIC F127), collagen, albumin,gelatin, cellulosics in nonaqueous solvents, and combinations of theabove and the like. Other binders include, for example, polypropyleneglycol, polyoxyethylene-polypropylene copolymer, polyethylene ester,polyethylene sorbitan ester, polyethylene oxide or combinations thereofand the like. Hydrophobic binders can also be used in the invention.

Film and its Properties

It will be understood that the term “film” according to this disclosureincludes thin films and sheets, in any shape, including rectangular,square, or other desired shape. The films described herein may be anydesired thickness and size suitable for the intended use. For example, afilm of the present disclosure may be sized such that it may be placedinto the oral cavity of the user. Other films may be sized forapplication to the skin of the user, i.e., a topical use. For example,some films may have a relatively thin thickness of from about 0.1 toabout 10 mils, while others may have a somewhat thicker thickness offrom about 10 to about 30 mils. For some films, especially thoseintended for topical use, the thickness may be even larger, i.e.,greater than about 30 mils. In addition, the term “film” includessingle-layer compositions as well as multi-layer compositions, such aslaminated films, coatings on films and the like. The composition in itsdried film form maintains a uniform distribution 5 of components throughthe application of controlled drying of the film.

Furthermore, the films of the present disclosure may have asubstantially uniform thickness because it is known that absence of auniform thickness detrimentally affects uniformity of componentdistribution throughout the area of a given film. Monitoring and controlof the thickness of the film also contributes to the production of auniform film by providing a film of uniform thickness. The thickness ofthe film may be monitored with gauges such as Beta Gauges. A gauge maybe coupled to another gauge at the end of the drying apparatus, i.e.,drying oven or tunnel, to communicate through feedback loops to controland adjust the opening in the coating apparatus, resulting in control ofuniform film thickness. Alternatively, the thickness of the film canalso be controlled by manual measurement during the production processto achieve the desired thickness of the film.

The film sheets of this disclosure may have various thicknessesdepending on the ingredients and matrix materials. The thickness of asheet can range from about 100 nm to about 500 microns. Nano-scalesheets can range from about 100 nm to about 1000 nm, from about 200 nmto about 900 nm, from about 300 nm to about 800 nm, from about 400 nm toabout 700 nm, or from about 500 to about 600 nm. The micron-scale sheetscan range from about 1 micron to about 500 microns, from about 10microns to about 250 microns, from about 20 microns to about 200microns, from about 30 microns to about 150 microns, from about 10 40microns to about 125 microns, from about 50 microns to about 100microns, from about 60 microns to about 90 microns, or from about 70microns to about 80 microns. However, it should be recognized that thesheets can have any thickness that allows for preparation into aningestible unit as described herein. In one example, each discrete sheethas a thickness less than 50 microns.

The film sheets may exist as thin strips with an area of roughly 1 in²and 4 mils thick, plus or minus 1%, 5%, 10%, 15%, 20%, 25% thereof. Thedimensions of such film sheets limit the total amount of drug that canbe contained therein. For example, CBD can be provided in doses of 0.1mg, 1 mg, 2 mg, 3 mg and 4 mg and 8 mg and 10 mg or up to 60 mg. Thisdosage film weight amount can be available in doses of 100 mg, 200 mg,or even 30 greater. Now, the film sheets can be prepared with a specificor maximum amount of agent contained therein.

The films can have various configurations and formats. The films mayhave a larger width and length compared to thickness. This provides atop surface and a bottom surface with a significant cross-sectionalprofile, but is relatively thin in order to be a sheet. The sheets maybe films, lamina, laminates, wafers, or other thin-body structures. Thefilms may range from about 100 nanometers to many microns in thickness.A sheet can be a lamina or a laminate of a plurality of lamina. Thelamina can be a layer that is combined with other lamina layers into alaminate. While the discrete sheets are described to be combined intolaminate structures, the individual sheets themselves can be prepared aslaminates from one or more types of thin lamina. The thin lamina can bea thin plate or layer of material, which often is of a sub-micron size.The lamina can be prepared into a laminate and used as a sheet. Thesheet can also be prepared as a wafer, which can be a thin member, suchas a thin disk, and may be a dried paste, gelatin adhesive paper, or thelike. Also, the wafer may be a thin sheet enclosing or containing apowder or particles, where the powder or particles can be a biologicallyactive agent.

The film sheets can be shaped while being formed or shaped after beingset. The laminates of the film sheets can also be cut into a specificshape before or after the film sheets are laminated together. Theshaping can include cutting, stamping, laser-shaping, or any othermethod of cutting a thin film or a stack of films.

In one example, the thin film sheets can be edible polymer films, suchas those that dissolve in the mouth. Such edible polymer films, whichcan be for delivery of pharmaceutical products, are commerciallyavailable. Widely-known examples of the edible polymer films include theListerine® PocketPaks strips sold as a dry, portable breath-refreshingproduct, the Gas-X® peppermint-flavored thin strips containingsimethicone as the active pharmaceutical ingredient (API), and the firstprescription pharmaceutical film strip, Zuplenz®, containing ondansetronas the API, which was approved by the U.S. FDA in 2010 for the treatmentof nausea following chemotherapy for example. These individual thin filmsheets are prepared for individual consumption. These thin film sheetproducts are designed as orally disintegrating films.

The film of the present disclosure may be divided into equally sizedunits having substantially equal amounts of each compositional componentpresent. This advantage is particularly useful because it permits largearea films to be initially formed, and subsequently cut into individualunits without concern for whether each unit is compositionally equal.For example, the films of the present disclosure have particularapplicability as delivery systems for agents from hemp and/or cannabisbecause each film unit will contain the proper amount of the agent. Thefilms may also have particular applicability as ingestible films, whichare dissolved in the mouth of the user, either rapidly or over acontrolled period of time. They may also be used for systemicadministration of agents by applying the films to oral or vaginalmucosal surfaces.

A self-supporting film dosage composition may include at least onecarrier or matrix (e.g., polysaccharide (pullulan) or polymer), and atleast one active agent (e.g., substance from hemp and/or cannabis). Theagent may be a small-scale particle such as a microparticle or ananoparticle, or individual molecules.

Emulsion and Use of the Same in the Preparation of a Film

The active agent (e.g., substance from hemp and/or cannabis) may beprepared into an emulsion that if formed into a film, such as an orallydissolving film, the agent may be present from less than 1% to greaterthan 60% by weight of the film.

The agent may be in a purified agent, such as greater than 90%, 94%, or99% in a crystal, isolate, or powdered form. The films and methods ofpreparing the emulsion or film can specifically exclude the use ofextracts, waxes or oils from hemp or cannabis. Instead, such extracts,waxes or oils from hemp or cannabis can be ultrapurified into thepowdered format described herein, which allows for accurate dosing ofthe agent in the emulsion and resulting film. The powdered agent can beobtained or prepared before inclusion in the emulsion. The powderedagent can include CBD and/or THC or other components from hemp orcannabis described herein, such as a crystalline form. The crystals canbe grainy and in a powder.

The general method 120 for the preparation of the film is shown in FIG.4 and ingredients used in the preparation of the film, in an exemplaryembodiment, is shown in Table 1 below.

Ingredients Percent of Strip Amount Mass/batch Active (in mg/strip) CBDIsolate 12-70 12000-70000 Matrix in mg/strip Pullalan 24-55 2400-5500Sucralose 1.5-3   150-300 Guar gum 2.5-4   250-400 Pectin 2-5 200-400Liquids in mL mL/batch Water ratio 2.25 25-50 Vanilla 15  3-15 Maskingagent 5 0.8-5  Permeability 10  1-10 enhancer (menthol) Polysorbate 10 1-10 Glycerin 5 0.4-5  Colorant 2 0.6-2  (Yellow) TOTAL 47 47

The method shows that a powdered agent is first prepared into anemulsion. The emulsion may be prepared from a surfactant (e.g.,polysorbate or the like) and a solubilizer 122 (e.g., glycerin or thelike) mixed together in an aqueous solution (e.g., water) 124. The agentis added to the surfactant, solubilizer, and water 126 to form theemulsion 130. Various emulsion preparation techniques can be used in theprocess, such as sonication, vibration, mixing, or the like. Thecomposition having the surfactant and solubilizer with the agent can beheated at temperature ranges of 70° F. to 250° F. (128), or 100E-170°F., or about 120° F. for a period of 5-45 minutes, or 10-35 minutes orabout 30 minutes to dissolve the agent and form the emulsion 130. Itwill be appreciated that the use of techniques such as vibration, vacuumand heat also aids in the efficient removal of air bubbles from theemulsion leading to a final homogenous emulsion. A suspension may alsobe formed. The emulsion may then be treated (132) with a sugar (e.g.,saccharide or the like) or sugar polymer (e.g., polysaccharide or thelike), such as pullulan or the like. Additionally, a dissolver (e.g.,pectin or the like) may be introduced into the emulsion. A thickener(e.g., guar gum or the like) may also be introduced into the emulsion. Ataste modifier, such as a sweetener (e.g., sucralose or the like) and apenetration enhancer may also be introduced into the emulsion. Otheringredients, such as flavoring agents (e.g., natural or artificial) orcoloring agents (e.g., natural or artificial) may be introduced into theemulsion. After modifying the emulsion with one or more of theabove-referenced modifiers, the resulting modified emulsion 134 may beprepared into the film having the agent.

The modified emulsion may then be degassed 136 prior to forming the filmto release any trapped air in the emulsion. The degassing can beperformed in open air or with vacuum; however, open air degassingwithout vacuum may be preferred to avoid loss of volatile substancesfrom the hemp and/or cannabis. The modified emulsion can be introducedin a vessel and then cast into a film 138.

Further processing of the emulsion may include any processing approachthat can result in a film. Examples of such processing may includeextrusion (FIG. 6), solution casting box apparatus (FIG. 5), reverseroll coating casting, and other solution casting apparatus' known tothose skilled in the art of solution casting. The modified emulsion canbe passed between rollers (e.g., casting rollers), and rolled onto asubstrate at the desired wet gauge thickness. The substrate can be a waxor silicone coated substrate that allows the film to be peeled therefromonce the film is stable. The rollers can be adjusted to change the gapthere between to change the wet gauge thickness of the film. Once on thesubstrate, the film can be cured and solidified, such as by heating. Inone example, the film on the substrate can be passed through a heater(e.g., infrared heater) with air flow to provide convection heating,which is regulated to remove moisture from the film. The film can beformed in this matter to inhibit rippling or other unfavorablecharacteristics, and may avoid blistering. Good throughout heating andcuring can produce the desired film.

The active (e.g., pure powdered CBD or THC) may be added to apolysorbate and glycerin mixture and heated up just a little bit to getthe active to dissolve. The glycerin is used as a solvent, and providesflexibility in the film. The polysorbate is used as a surfactant andcreates a suspension when added to water and provides a suspension ofCBD. Pullulan is then added, which as a sugar polymer forms into amatrix and provides the final emulsification. So the combination of thepolysorbate, the Pullulan and the glycerin allow the CBD and/or THC tobe dissolved or suspended into water uniformly as an emulsion. ThePullulan locks the active into sugar matrix and the entire solutionbecomes a uniform homogenous emulsion. Additional additives such aspectin and guar gum and sucralose may be added. The guar gum is used tothicken the solution which is helpful for the casting process. Thepectin is used because it provides good dissolvability for the film andsome structural properties. The sucralose is used as a sweetener andflavoring. Optionally, we can add any desirable flavors to improve thetaste and food coloring agent for aesthetics. The emulsion having thepolysorbate, Pullulan and glycerin allows the CBD and/or THC to besuspended uniformly and homogenously so that the right amount of CBDand/or THC is included in each film strip.

The method of preparing an emulsion composition may also includeproviding an aqueous-based emulsion and converting the aqueous-basedemulsion into a non-aqueous dry emulsion, wherein the dry emulsion is inthe form of a self-supporting film. The method further includesdissolving the film with an aqueous solvent, thereby reforming theaqueous-based emulsion. Another method of preparing an emulsioncomposition includes providing a solid water soluble polymeric filmhaving dispersed therein an active agent; and adding water to dissolvethe film, thereby forming an emulsion.

Moreover, the disclosure also provides a method of preparing a film fordelivery of an active. The method includes preparing a compositionincluding at least one water soluble polymer; a polar solvent (water);and an emulsion composition that includes the active; and forming a filmfrom the prepared composition. The method further includes drying thefilm by a process whereby the active become dispersed within the film.Also provided is a method of preparing a water reconstitutable emulsioncomposition. The method includes preparing a composition including atleast one water soluble polymer; a polar solvent; and an emulsioncomposition. The method also includes drying the composition to form adry emulsion including active agent within a solid water solublepolymeric matrix.

In one embodiment, the film can be prepared to have a specific amount ofbiologically active agent, such as a specific amount of drug. The amountof drug included should be consistent across a number of batches so thatthe ingestible unit can achieve regulatory compliance. Accordingly, themethod of preparing an ingestible unit can include: preparing acomposition having a biologically active agent at a defined amount;forming the composition into a discrete sheet to have the biologicallyactive agent at a defined amount; and including the discrete sheet in apackage. The method may also include: determining a dose of abiologically active agent to be included a film. Drug loading intosheets can be up to about 70% by weight of the sheet, and often up toabout 50% by weight. The amount of drug in each sheet can be calculatedbefore or after shaping the individual sheets or ingestible unit intothe size and shape of the dosage form. The amount of drug lost duringprocessing can also be taken into account in order to design theingestible units and select the appropriate number of sheets to arriveat the predetermined dose. However, it should be recognized that asingle sheet may be suitable for the entire dose of an ingestible unit.The same methodologies can be performed when the ingestible unitincludes two or more different biologically active agents. Moreover,this methodology can be used for determining the amount of any agent oringredient described herein.

The emulsion technology used to prepare the film of the presentdisclosure has a greater advantage in terms of accurate dosing of thefilm. Specifically, the use of a lipid or fat based emulsion systemallows for more accurate dosing that may vary only by ±2% or lower. Onthe other hand, the dosing of prior art films may vary widely by >3%or >5% or >10% or >50%. This is because the prior art compositions relyon simple extracts from cannabis or hemp that contain oils, waxes andother plant raw materials that hinder the preparation of a homogenousemulsion or they may dissolve the CBD or THC in alcohol or fat and thenplace into an emulsion to prevent separation, or the active agents leachout of the film during the process. All these may result in veryinaccurate dosing of the active agent in the film.

Once the film is formed over a substrate such as wax or silicone (FIG.3), the film may be separated from the substrate. Such separation caninclude peeling, slicing, or parting the film from the substrate. Thefilm may then be cut into desired sizes, such as the sizes describedherein. The cut film may then be packaged for use. The packaging may befor individual films or in a dispenser that dispenses single films froma film stack such as varying the dimensions of the individual film dosestrip. In one example, the individual film can be packaged between twofoil layers (FIG. 3A), and then placed into an individual package. Touse, a user can open the package, remove the foil layers, and place thefilm in the mouth. Vaginal or rectal administration may also beperformed.

In one example, the film may be 4 mils thick and 1 inch by 1 inchsquare. If prepared properly, this configuration can be a 100 mg filmhaving 10 mg active, such as CBD and/or THC. However, the active can beformulated to be up to about 60% of the film to provide 60 mg active.Also, a 60 mg per 130 mg film may also be prepared. Also, a prepared 10mg CBD film will be less than or more than 100 mg. The individual filmsmay be evaluated by weight or have other characterizations to accuratelydetermine the amount or concentration of the active in the film. A filmdoes not have a set ratio of active to inactive ingredients. (e.g., Afilm may contain 1 mg of active with a total weight of 100 mg.)

It should be recognized that the substances described above may besubstituted with other equivalent substances. For example, starches maybe used.

Preparation of a Film and Film Casting

The emulsion prepared as described above may be taken from the existingmixing vessel or put into a run tank vessel and then is cast on a line.The process may use a very unique reversal roll method between twostainless steel rollers. The casting roller in the front dictates thespeed of the line. A wax coated carrier paper or silicone paper or othercoated or uncoated paper or other material starts at the casting box andcan be used to carry the film forming composition through the oven. Thefilm is cast at the desired thickness to get a final thickness, and itgoes through an infrared heater system, which has convection air flowingthrough from an exhaust fan to help draw the moisture off the film. Goodconvection air flow in the tunnel that keeps the moisture coming off ata constant rate and as long as the line speeds matched with thetemperature settings correctly, the process provides good uniform dryingthat doesn't have underneath wet spots under the film top layer.

The film is cast at the desired wet thickness to get the desired finalthickness of the partially or completely dehydrated film. The film isdehydrated as it is carried through an infrared heater system, that hasconvection air flowing through from an exhaust fan to help draw themoisture off the film. By generating adequate convection air flowthrough the oven tunnel, moisture is evaporated from the film at aconstant rate. When the speed of drying and the temperature settings aresufficiently matched, the end result is an evenly dried film. Thiscontrolled heating and uniform heat application prevent the film fromdrying at an uneven pace which may cause a dried exterior covering wetfilm. The dried film is collected on a spool containing the carrierpaper (or other carrier medium) and the film at the end of the ovensystem. The carrier paper and film are then transferred to anothermachine to perform the cuts that create one inch bobbins. The bobbinsize may vary to accommodate various dosages. From the cutting machine,a bobbin is then transferred to a packaging machine. The packagingmachine peels the film away from the carrier paper and then cutsindividual strips of film and places each piece between two foil layers.The foil is then heat sealed on all sides to protect the individualfilms.

Also, the dried film can be obtained at the other end of the oven on aroll system, to provide a finished roll of dissolving film on top of thewax or silicone paper. The paper having the film goes through a slittingprocess from the bulk roll into bobbins ranging from widths of ½″ to 1¾″inches depending on the dosage level, and then that bobbin goes onto apackaging machine that individually cuts the film to size based on thedosage amount. The cut film gets packed between two protective foillayers, and the foils are heat sealed around the film, and thenindividually packed.

The following protocol is only one example of how to make the filmsdescribed herein. The emulsion mixture used for film formation isprepared as such. The reaction vessel is set to a temperature of 90° F.through the use of recirculated water through the water jacket on thereaction vessel. Deionized water is added to the vessel, and themechanical stirrer is set to approximately 300 RPM (this can vary). Fromthis point on the reaction vessel should always be sealed to ensure thatminimal amounts of water and volatiles escape, and to ensure that nocontaminants enter the reaction vessel, only remove the stopper to addingredients. The active compound, in this case purified CBD crystalisolate powered are used. In a separate glassware/container/vessel, theactive compound, in this case purified CBD, is added to a mixture ofpolysorbate (or other surfactant/emulsifier) and vegetable glycerin (orother carrier solvent/softening agent) and the mixture is mixed untilthe active compound is dissolved. Heat, up to 500° F., or preferably upto 380° F. can be applied to the mixture to aid in the formation of aneven mixture with the active compound dissolved and/or distributedevenly. The flavoring agents can also be included into this solution tohelp increase the volume and aid in dissolvability, or the flavoringagents can be added directly to the reaction vessel. Assuming thatflavoring agents were also added to the mixture of active compound,vegetable glycerin, and polysorbate, the entire mixture is then slowlyadded to the reaction vessel containing water up to this point and beingstirred via mechanical stirrer. Continue to stir mixture to ensureuniform distribution of added solution and thus the formation of ahomogenous emulsion. Next, the pullulan is added slowly to thicken thesolution and lock the homogenous mixture into a polysaccharide matrix.

Once the mixture is uniform and all of the pullulan (or otherpolysaccharide or film former) has been added, the remaining thickeningagents can be added, and at this point the stirring might need to beincreased to 500 RPM (this can vary). The pectin (or other thickeningagent) is added to the mixture, and then guar gum (or other thickeningagent) is added. Continue to stir the solution to ensure a homogenousmixture. Add the sucralose (or other sweetener) to the mixture andensure that all of it is mixed into solution. Finally, the food coloringis added to desired color, and the mixture continues to stir to evenlydistribute the color.

At this point the solution contains a good amount of air in solution dueto mixing and two options are available. Option 1, the stirring isslowed down and the entire reaction vessel is placed under vacuum topull the air from the mixture, and is kept under vacuum until no furtherexpansion of the mixture is visible. The vacuum is then stopped, and thesolution is collected from the reaction vessel ready to cast. Option 2,the mixture is collected from the reaction vessel and is collected intoa container and sealed, and left for several hours to degas, this ismainly possible due the unique mixture of the above ingredients, and isnot typical of such emulsions. The following day the mixture is ready tobe cast.

The mixture is cast by any method known to those skilled in the art ofsolution casting, such as the roller method described herein. As shownin FIG. 1 the film of the present disclosure may contain a matrix andthe active dispersed therein. Alternatively, the insoluble activeparticles may be impregnated in the film matrix as shown in FIG. 2.

In one particular example, pure CBD crystal isolate powder was dissolvedin solution by 30 placing flavor, polysorbate, and vegetable glycerinand heating in a temperature range of 70° F. to 250° F., or 100° F.-170°F., or about 120° F. for a period of 5-45 minutes, or 10-35 minutes orabout 30 minutes to create a homogenous emulsion. After the mix wasvisually inspected to ensure it was sufficiently blended, the emulsionmix was pipetted into the mixing vessel that already contained waterheated to 90° F.

The following substances may also be used in the preparation of thefilms.

Surfactant/emulsifier: Polysorbate 20 (polyoxyethylene (20) sorbitanmonolaurate); Polysorbate 40 (polyoxyethylene (20) sorbitanmonopalmitate); Polysorbate 15 60 (polyoxyethylene (20) sorbitanmonostearate); Polysorbate 80 (polyoxyethylene (20) sorbitanmonooleate); Polyethylene glycol; Monoglycerides; Diglycerides;Triglycerides; Phospholipids; Lecithin; Sodium bis(2-ethylhexyl)sulfosuccinate (AOT); or sodium mono- and dimethylnaphthalene sulfonate(SMDNS).

Carriers/softening agents: Glycerol/glycerin; Propylene Glycol; Fattyacids; 20 Vegetable oil; Vegetable shortening; Olive oil; Soybean oil;Grape seed oil; Sunflower oil; Peanut oil; Corn oil; Canola oil; RiceBran oil; Lard; Suet; Butter or Coconut oil.

Polysaccharides and thickening agents: Acetylated distarch adipate;Agar; Alginic acid; Arrowroot; Beta-glucan; Calcium alginate;Carrageenan; Cassia Gum; Chondrin; Collagen; Corn starch; Dextrin;Disodium phosphate; Disodium pyrophosphate; 25 File powder;Galactomannan; Gelatin; Gellan Gum; Glucomannan; Guar Gum; Gulaman; GumKaraya; Hydroxypropyl distarch phosphate; Hypromellose; Irvingiagabonensis; Konjac; Kudzu; Locust; Bean gum; Maltodextrin; MethylCellulose; Millet Jelly; Modified starch; Monodora pyristica; Monosodiumphosphate; Mung bean; Natural Gum; Njangsa; Pullulan, Pectin; Phosphatedistarch; phosphate; Polydextrose; Potassium 30 bitartrate; Potatostarch; Psyllium seed husks; Sago; Salep; flour; Sodium phosphate;Starch; Tapioca; Tetrasodium pyrophosphate; Tragacanth; Trisodium;phosphate; Waxy corn; or Xanthan gum.

Sucralose Alternatives: Artificial Sweeteners: Acesulfame-K; Advantame;Alitame; Aspartame; Crystalline Fructose; Cyclamate; Cyclamates;Dextrose; Fruit Juice Concentrates; Glucose Syrup; High Fructose CornSyrup; Honey; Maltodextrin; Neohesperdine; Neohesperidin DC; Neotame;Saccharin; Thaumatin; Natural Sweeteners: Brazzein; Curculin; DouxMatokSugar; Fructose; Galactose; Glucose; 5 Glycyrrhizin; Lactose; Levulose(Fructose); Luo; Han Guo; Maltose; Miraculin; Monatin; Monellin; MonkFruit (Luo Han Guo); Pentadin; Saccharose; Stevia; Stevioside; Sucrose;Sugar; Yacon Syrup; Sugars: Agave Syrup; Barley Malt; Syrup; Brown RiceSyrup; Caramel; Corn Sugar (HFCS); Corn Sweetener (HFCS); 1 Corn Syrup(HFCS); Fructose Glucose Syrup (HFCS); Glucose Fructose Syrup (HFCS);Golden Syrup; HFCS,42; HFCS 10,55; HFCS,90; High Fructose Corn Syrup(HFCS); High Maltose Corn Syrup (HMCS); Inverted Sugar; Isoglucose(HFCS); Modified Sugar; Refiners Syrup; Tagatose; Trehalose; SugarAlcohols/Polyols: D-Tagatose; Erythritol; Glucitol (Sorbitol); Glycerol;HSH; HSH Hydrogenated Starch Hydroslsates; Hydrogenated StarchHydrolysate (HSH); Isomalt (Palatinat); Lacititol; Maltitol; Mannitol;Polydextrose; Sorbitol; Xylitol; Sugar 15 Extracts: Birch Syrup;Blackstrap Molasses; Cane Juice; Coconut Palm Sugar;Fructooligosaccharide; Inulin; Isomalto, oligosaccharide (IMO); MapleSyrup; Molasses; Oligofructose; Palm Sugar; Rapadura; Sorghum Syrup; orSugar Fiber.

The preparation of the film of the present disclosure may involve anyone of the following processes. As shown in FIG. 5 the process mayinvolve a simple casting procedure. This includes a liquid composition210 having a carrier 212 and an agent 214, which is cast into asubstrate 216, and prepared into a thin film sheet 218. The casting canbe into a substrate 216 that is a shaped mold or a flat plate as shownfor amorphous casting. The liquid composition 210 can have ingredientsthat are preselected to provide a thin film sheet 218 that has one ormore predetermined functionalities. The casting can include any castingsteps for casting a polymeric composition into a thin film. The carrier212 can be any type of carrier that can be cast into a thin film orother sheet as described herein. The agent 214 can be any type ofchemical agent or agent particulate.

It should be noted that the same basic method depicted in FIG. 5 may beused for casting films, whether they have different drug load, differentdrug particle size, or if they are made from different polymers, or fromdifferent grades of a given polymer.

The film may also be prepared by extrusion process as shown in FIG. 6.This procedure 220 can include introducing a liquid composition 210 intoa hopper 222 that feeds into a screw auger mixer 224 in an extruder 226for extruding the liquid composition 210 into an extrudate 230. Theextrudate 230 may optionally be cut or pressed into a sheet of theinvention. However, the extrudate 230 can be passed through a sizingplate 232 to form sized extrudate 235 that can be cut into a sheet ofthe invention. The extrudate 230 is shown to be cooled with a water tank234 jacketing the sizing plate 232, so that the extrudate 230 can becooled, if needed, while being dimensioned. The sized extrudate 235 canbe processed through one or more rollers 236 so as to calender theextrudate into a thin film 237. The thin film 237 can then be cut with acutting machine 238 into individual thin film sheets 240.

The film of the present disclosure may also be prepared as molded thinfilms as shown in FIG. 7. A mold array 252 having a plurality of molds254 can receive a liquid composition 210 in order to form the moldedthin films 256 dimensioned and shaped as the mold 254. As such, eachmold can be shaped to have a specific cross-sectional width and lengthand a specific depth in order to have a specific volume and shape. Thedepth can be thin as a film or thickness dimension described herein. Theshape can be rectangular as shown as well as being circular, oval,triangular, square, or any other polygon or any other shape ranging fromstars, hearts, or other simple shapes to complex shapes, such as animal,plant, or the like.

The film sheets can be shaped while being formed or shaped after beingset. The laminates of the film sheets can also be cut into a specificshape before or after the film sheets are laminated together. Theshaping can include cutting, stamping, laser-shaping, or any othermethod of cutting a thin film or a stack of films.

The present disclosure also provides a method of forming aself-supporting film dosage composition, including the steps ofproviding a carrier (e.g., polysaccharide or polymeric) matrix,providing at least one active agent, dispersing the agent throughout thematrix, and drying the matrix so as to form a self-supporting filmdosage composition including agent. The agent may be in the form of asingle molecule, microparticle or a nanoparticle. The film may be formedthrough emulsion processing, through milling, and/or through amicrofluidics pumping apparatus. In some embodiments, the active may beformed via a high shear apparatus.

There is also provided a self-supporting film that includes a watersoluble polymer composition including polyethylene oxide or asaccharide-based polymer. The film may also include a small scale formof the active agent. In some aspects, the film may be designed for oraladministration. In other aspects, the film may be designed for mucosal(e.g., oral, vaginal, rectal) administration. As will be described infurther detail below, the film is desirably substantially dissolvablewhen exposed to a wetting agent, such as water, alcohol or aqueousmixture of alcohols.

Each of the films prepared according to the present disclosure may bedivided into smaller individual film units which may be sized andpackaged to provide dosage units for consumption. The disclosure alsoprovides a method of delivering an active agent. This method includesproviding a dry film, which at least partially solubilizes when wetted,the film comprising (i) a water soluble composition; (ii) an activeagent and (iii) administering the film to the user. The water solublecomposition may include a saccharide-based polymer. Also provided is aself-supporting film for delivery of an active agent. This film mayinclude a solid water soluble polymeric matrix having dispersed thereina plurality of lipophilic droplets formed from an emulsion compositionhaving the agent. An ingestible film unit may have one discrete sheetthat includes a biologically active agent.

The biologically active agent can be any agent that is administered fora function, such as a biological function to improve or otherwisemodulate a biological process, such as a biological pathway. As such,the biologically active agent can be a traditional pharmaceutical ornutraceutical, and it can be any type of substance for testing ordiagnostics. The biologically active agent can be any agent that isadministered to a subject, human or animal, in order to elicit abiological response that arises from the biological activity of theagent. The biological response obtained can be a measurable biologicalresponse or provide some change that can be analyzed and determined,such as by testing to determine an amount of the biologically activeagent to be administered. The biologically active agent can be a toxinor poison or other deleterious substance. Examples can include thebiologically active agent being a mineral, vitamin, pharmaceutical,nutraceutical, small molecule, macromolecule, organic molecule,polypeptide, protein, nucleic acid, polynucleotide, derivatives thereof,and combinations thereof. The biologically active agent can be for ahuman or animal subject. Human and veterinary medicines can be improvedwith the present invention. Alternatively, each discrete sheet can bedevoid of a biologically active agent when the ingestible unit is aplacebo. Substances from hemp or cannabis, such as CBD or THC may beexamples.

The films may be prepared from any type of film or laminate formingmaterial. That is, any material that can be formed into a thin film canbe used as a sheet having a particular function of the presentinvention. The film-forming material can range from polymers that arenatural or synthetic. However, the film-forming material may be asubstance other than a polymer. In one example, the film-formingmaterial can be calcium phosphate, talc, calcium silicate, calciumcarbonate, derivatives thereof, and combinations thereof, where calciumembodiments may be formed into laminates. In one example, thefilm-forming material can be a carrageenan.

The films may also be formed from an inorganic component. The inorganiccomponent can be prepared into a laminate sheet. Some non-limitingexamples of inorganic components that can be prepared into the discretesheets include calcium phosphate, calcium silicate, calcium carbonate,derivatives thereof, and combinations thereof. Some inorganic materialscan be formed into ceramic thin films or laminates.

The film units of the present disclosure may include at least one watersoluble polymer. The films may also include water swellable or waterinsoluble polymers, if desired.

The self-supporting film may also include a saccharide-based polymer,which is water soluble. For example, the saccharide-based polymer may becellulose or a cellulose derivative. Specific examples of usefulsaccharide-based, water soluble polymers include, but are not limitedto, polydextrose, pullulan, hydroxypropylmethyl cellulose (HPMC),hydroxyethyl cellulose (HPC), hydroxypropyl cellulose, carboxymethylcellulose, sodium aginate, xanthan gum, tragancanth gum, guar gum,acacia gum, arabic gum, starch, gelatin, and combinations thereof

The saccharide-based polymer may be at least one cellulosic polymer,polydextrose, or combinations thereof. The film may also includenon-saccharide-based, water soluble or water insoluble polymers.Examples of non-saccharide based, water soluble polymers includepolyethylene oxide, polyvinylpyrrolidone, polyvinyl alcohol,polyethylene glycol, polyacrylic acid, methylmethacrylate copolymer,carboxyvinyl copolymers, and combinations thereof. Specific examples ofuseful water insoluble polymers include, but are not limited to, ethylcellulose, hydroxypropyl ethyl cellulose, cellulose acetate phthalate,hydroxypropyl methyl cellulose phthalate and combinations thereof.

The polymer may also be a combination of substances, such ashydroxypropylmethyl cellulose and polyethylene oxide; polydextrose andpolyethylene oxide or polydextrose, hydroxy propylmethyl cellulose andpolyethylene oxide.

As used herein, the phrase “water soluble polymer” and variants thereofrefer to a polymer that is at least partially soluble in water, anddesirably fully or predominantly soluble in water, or absorbs water.

The film unit of the present disclosure is at least partiallydissolvable when exposed to a wetting agent or may be substantiallydissolvable when exposed to a wetting agent. The film of the presentdisclosure may be absorbed through the mucosal tissue within about 20seconds, or about 30 seconds, or about 40 seconds or about 60 seconds.Unlike prior art films which dissolves very quickly or instantaneouslyin the mouth allowing the active agents to break down in the digestivetract, the film of the present disclosure dissolves slowly so that thebulk of the active agent seeps through the mucosal tissue of thesubject.

Polymers that absorb water are often referred to as being waterswellable polymers. The materials useful with the present invention maybe water soluble or water swellable at room temperature and othertemperatures, such as temperatures exceeding room temperature. Moreover,the materials may be water soluble or water swellable at pressures lessthan atmospheric pressure. Desirably, the water soluble polymers arewater soluble or water swellable having at least 20 percent by weightwater uptake. Water swellable polymers having a 25 or greater percent byweight water uptake are also useful. Films or dosage forms of thepresent invention formed from such water soluble polymers are desirablysufficiently water soluble to be dissolvable upon contact with bodilyfluids.

Other polymers useful for incorporation into the films of the presentdisclosure include biodegradable polymers, copolymers, block polymersand combinations thereof. Among the known useful polymers or polymerclasses which meet the above criteria are: poly(glycolic acid) (PGA),poly(lactic acid) (PLA), polydioxanoes, polyoxalates, poly(α-esters),polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters),polyamino acids, polyaminocarbonates, polyurethanes, polycarbonates,polyamides, poly(alkyl cyanoacrylates), and mixtures and copolymersthereof. Additional useful polymers include, stereopolymers of L- andD-lactic acid, copolymers of bis(p-carboxyphenoxy) propane acid andsebacic acid, sebacic acid copolymers, copolymers of caprolactone,poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers,copolymers of polyurethane and (poly(lactic acid), copolymers ofpolyurethane and poly(lactic acid), copolymers of α-amino acids,copolymers of α-amino acids and caproic acid, copolymers of α-benzylglutamate and polyethylene glycol, copolymers of succinate andpoly(glycols), polyphosphazene, polyhydroxy-alkanoates and mixturesthereof. Binary and ternary systems are contemplated.

Other specific polymers that may be suitable include those marketedunder the Medisorb and Biodel trademarks. The Medisorb materials aremarketed by the Dupont Company of Wilmington, Del. and are genericallyidentified as a “lactide/glycolide co-polymer” containing “propanoicacid, 2-hydroxy-polymer with hydroxy-polymer with hydroxyacetic acid.”Four such polymers include lactide/glycolide 100 L, believed to be 100%lactide having a melting point within the range of 338°−347° F.(170°−175° C.); lactide/glycolide 100 L, believed to be 100% glycolidehaving a melting point within the range of 437°−455° F. (225°−235° C.);lactide/glycoli 85/15, believed to be 85% lactide and 15% glycolide witha melting point within the range of 338°−347° F. (170°−175° C.); andlactide/glycolide 50/50, believed to be a copolymer of 50% lactide and50% glycolide with a melting point 30 within the range of 338°−347° F.(170°−175° C.).

Although a variety of different polymers may be used, it is desired toselect polymers to provide a desired viscosity of the mixture prior todrying. For example, if the topical agent or other components are notsoluble in the selected solvent, a polymer that will provide a greaterviscosity is desired to assist in maintaining uniformity. On the otherhand, if the components are soluble in the solvent, a polymer thatprovides a lower viscosity may be preferred.

The polymer plays an important role in affecting the viscosity of thefilm. Viscosity is one property of a liquid that controls the stabilityin an emulsion, a colloid or a suspension. Generally, the viscosity ofthe matrix will vary from about 400 cps to about 100,000 cps, preferablyfrom about 800 cps to about 60,000 cps, and most preferably from about1,000 cps to about 40,000 cps. Desirably, the viscosity of thefilm-forming matrix will rapidly increase upon initiation of the dryingprocess. The viscosity may be adjusted based on the selected agentcomponent, depending on the other components within the matrix. Forexample, if the component is not soluble within the selected solvent, aproper viscosity may be selected to prevent the component from settlingwhich would adversely affect the uniformity of the resulting film. Theviscosity may be adjusted in different ways. To increase viscosity ofthe film matrix, the polymer may be chosen of a higher molecular weightor crosslinkers may be added, such as salts of calcium, sodium andpotassium. The viscosity may also be adjusted by adjusting thetemperature or by adding a viscosity increasing component. Componentsthat will increase the viscosity or stabilize the emulsion/suspensioninclude higher molecular weight polymers and polysaccharides and gums,which include without limitation, alginate, carrageenan, hydroxypropylmethyl cellulose, locust bean gum, guar gum, xanthan gum, dextran, gumarabic, gellan gum and combinations thereof

When the active agent is a biologically active agent oranti-counterfeiting agent, then it may be included as particles in thediscrete sheets. The particles can be embedded entirely within the sheetmatrix or embedded in a surface to provide a rough profile. Someparticles may be exposed in the surface. The particles can be obtainedor prepared by aggregating a number of agent molecules together. Thesize of the particles can vary or be uniform. Preferred particle sizescan range from about 10 nm to about 1000 microns, from about 1 micron toabout 50 microns, and from about 10 microns to about 100 microns. Also,the sheets having the particles can be prepared on-site or obtained froma supplier. The sheets can be made by: preparing a plurality ofparticles having a biologically active agent; suspending the pluralityof particles in a composition; and forming the composition into adiscrete sheet. The sheets can include a high load of particles, whichcan be about 50% by weight or +/−10% or 20%. This can allow for theingestible unit to include as much drug as current tablets or capsules,which can be over 1000 mg in some instances, but usually containing lowhundreds of milligrams. The sheets can include a low load of particles,which can be about 5% to 1% by weight. The sheets can include a very lowof particles, which can be about 1% or less.

The biologically active agent can also be a nutritional supplement, suchas iron, which is difficult to administer with proper absorption. Ironis soluble in acidic pH, and usually precipitates in the intestine atneutral pH. Now, one or more pH-modifying sheets that produce an acidicenvironment or microenvironment can be included with the iron sheet.Similarly, other specific functionalities can be provided to improve theabsorption of biologically active agents. Also, complexing and/orchelating agents can be included in sheets to complex with agents tofacilitate absorption from the intestine.

Treatment of Disorders

The disintegration of the film can occur within about 60 seconds uponcoming in contact with water, such as the saliva, stomach fluid, ordelayed to occur in the small or large intestines. The disintegrationmay also occur immediately upon coming in contact with saliva, producinga predefined breakage pattern into smaller pieces for easier mucosaldelivery.

The film strips described herein having the CBD and/or THC can be usedfor treatments known in the art. CBD could be used for treating symptomsof rheumatoid arthritis and other autoimmune diseases, diabetes, nausea,bowel disorders, inflammation, provide neuroprotective effects, andprovide anti-cancer effects, and reduce many other hard-to-control sideeffects of other medications. THC can be used to treat aches, pains,backache, muscle stiffness, joint pain, inflammation, and reduce manyother hard-to-control side effects of other medications or anticancertreatments. The THC can be used to provide anti-emetic, appetiteenhancing, relaxation, analgesia, and therapeutic use in Tourette'ssyndrome, treat dystonia and tardive dyskinesia, treat nausea, treatvomiting, treat anorexia, treat cachexia, treat spasticity, treatmovement disorders, treat Multiple Sclerosis, treat pain (rheumatoidarthritis, cancer pain, headache, menstrual pain, chronic bowelinflammation and neuralgias), treat glaucoma, treat epilepsy, treatasthma, treat addiction, treat substance dependency, treat withdrawalsymptoms, treat psychiatric symptoms, treat autoimmune diseases, treatinflammation (e.g. ulcerative colitis, arthritis), 10 and many others,and may be used to treat pruritis, hiccup, attention deficit syndrome,high blood pressure, tinnitus, chronic fatigue syndrome, restless legsyndrome, insomnia, depression, anxiety, stress, situational sadness(e.g., from death in family), and any others.

One skilled in the art will appreciate that, for this and otherprocesses and methods disclosed herein, the functions performed in theprocesses and methods may be implemented in differing order.Furthermore, the outlined steps and operations are only provided asexamples, and some of the steps and operations may be optional, combinedinto fewer steps and operations, or expanded into additional steps andoperations without detracting from the essence of the disclosedembodiments.

1. A film comprising: an emulsion of an extract of cannabis; pullulan;hydroxypropylmethyl cellulose acetate succinate; and a flavorant ortaste masking agent, wherein the film is mucosally dissolvable.
 2. Thefilm of claim 1, wherein the emulsion is a lipid based emulsion, and thefilm comprises medium chain triglycerides from coconut oil.
 3. The filmof claim 2, wherein the medium chain triglycerides comprise capric acidand/or caprylic acid.
 4. The film of claim 1, comprising pectin and guargum.
 5. The film of claim 1, wherein the flavorant or taste maskingagent comprises vanilla, bubble gum, fruit flavor, mint, chocolate,licorice, marshmallow, peanut butter, aspartame, sucralose, sucrose,glucose, citric acid, stevia plant, kleptose, cyclodextrin, cyclodextrinderivatives, ginger, anise, cinnamon, peppermint, licorice, fruit juice,sweeteners, fructose, mannitol, saccharin, honey, or any combinationthereof.
 6. The film of claim 1, wherein the extract of cannabisconsists essentially of cannabinoids and/or tetrahydrocannabinol in aconcentration range from about 70% to about 100%, about 80% to about100%, about 90% to about 100%, about 95% to about 100%, or about 98% toabout 100%.
 7. The film of claim 1, wherein the extract of cannabis isin a range from about 1% to about 70% by weight of the film.
 8. The filmof claim 1, comprising a permeability enhancer, wherein the permeabilityenhancer comprises calcium chelators, polycarboxylic acids, zonulaoccluding toxin, poly-L-arginine, chitosan derivatives, niacin, omega 3or 6 fatty acids or other fatty acids, menthol, sodium caprate, sodiumdeoxycholate, dipotassium glycyrrhizinate, furanocoumarins andgrapefruit derivatives, bile salts, ethylenediaminetetraacetic acid,tocopheryl polyethyleneglycol succinate (TPGS), derivatives thereof, orany combination thereof.
 9. The film of claim 8, wherein thepermeability enhancer is in an amount of about 0.001% to about 10% byweight of the film.
 10. The film of claim 1, comprising a solubilizer, athickener, a surfactant, a coloring agent, a flavorant, an effervescentagent, an antioxidant, a bioadhesive agent, a pH modifying agent,vitamins, minerals, a dietary supplement, or any combination thereof.11. The film of claim 10, wherein the surfactant comprises sodium laurylsulfate, poloxamers, sorbitan esters, polysorbates, sorbitans, stearicacid derivatives thereof, or any combinations thereof.
 12. The film ofclaim 1, comprising an edible synthetic polymer, wherein the ediblesynthetic polymer comprises hydroxyethylcelulose, cellulose acetatephthalate, hydroxypropyl methylcellulose phthalate, carboxymethylethylcellulose, polyvinyl acetate phthalate, maltodextrin, dextran,hydroxypropyl cellulose, sodium carboxymethyl cellulose,poly(methacrylic acid-co-ethyl acrylate), poly(methacrylicacid-co-methyl methacrylate), poly(methacrylic acid-co-ethyl acrylate),poly(methacrylic acid-co-methyl methacrylate), polyvinylpyrrolidone,polylactic acid (PLA), poly-L-lactide (PLLA), poly-D-lactide (PLDA),poly(lactic-co-glycolic acid) (PLGA), or any combination thereof. 13.The film of claim 1, comprising an edible natural polymer, wherein theedible natural polymer comprises methylcellulose,hydroxypropylmethylcellulose, ethylcellulose, sodium alginate, starch,tapioca, chitosan, chitin, agar, derivatives, or any combinationthereof.
 14. The film of claim 1, wherein the film has a thicknessranges from about 0.00254 millimeters (mm) to about 0.762 mm.
 15. Thefilm of claim 1 is packaged with a foil on each of the two sides of thefilm to form a single packet.
 16. A film comprising: an emulsion of anextract of cannabis; pullulan; hydroxypropylmethyl cellulose acetatesuccinate; pectin; guar gum; medium chain triglycerides from coconutoil; and a flavorant or taste masking, wherein the film is mucosallydissolvable.
 17. The film of claim 16, wherein the flavorant or tastemasking agent comprises vanilla, bubble gum, fruit flavor, mint,chocolate, licorice, marshmallow, peanut butter, aspartame, sucralose,sucrose, glucose, citric acid, stevia plant, kleptose, cyclodextrin,cyclodextrin derivatives, ginger, anise, cinnamon, peppermint, licorice,fruit juice, sweeteners, fructose, mannitol, saccharin, honey, or anycombination thereof.
 18. The film of claim 16, wherein the extract ofcannabis consists essentially of cannabinoids and/ortetrahydrocannabinol in a concentration range from about 70% to about100%, about 80% to about 100%, about 90% to about 100%, about 95% toabout 100%, or about 98% to about 100%, and the extract of cannabis isin a range from about 1% to about 70% by weight of the film.
 19. A filmcomprising: an emulsion of an extract of cannabis; pullulan;hydroxypropylmethyl cellulose acetate succinate; pectin; guar gum;coconut oil or medium chain triglycerides; and vanilla, bubble gum,fruit flavor, mint, chocolate, licorice, marshmallow, peanut butter,aspartame, sucralose, sucrose, glucose, citric acid, stevia plant,kleptose, cyclodextrin, cyclodextrin derivatives, ginger, anise,cinnamon, peppermint, licorice, fruit juice, sweeteners, fructose,mannitol, saccharin, or honey, wherein the film is mucosallydissolvable.
 20. The film of claim 19, wherein the extract of cannabisconsists essentially of cannabinoids and/or tetrahydrocannabinol in aconcentration range from about 70% to about 100%, about 80% to about100%, about 90% to about 100%, about 95% to about 100%, about 98% toabout 100%, and the extract of cannabis is in a range from about 1% toabout 70% by weight of the film.